ABSTRACT Background A very high‐power short‐duration (vHPSD) radiofrequency (RF) ablation creates shallower lesions, which may be insufficient in thick myocardial regions. Aims To clarify an effective ablation strategy following the initial vHPSD application and determine the best approach to create sufficient lesion depth in thick myocardial regions using ex vivo and in vivo models. Methods Lesion metrics were compared under various settings: 35 W versus 50 W with the same target ablation index (AI) (Step 1); double vHPSD ablations versus vHPSD followed by AI‐guided ablation (Step 2); double applications (DA) with vHPSD followed by AI‐guided ablation with a target AI of 450 versus single application (SA) with a target AI of 550 at 50 W (Step 3). Results Lesion depth was comparable between groups with the same AI but different RF powers. Lesions were significantly deeper in the vHPSD ablation followed by a target AI of 450 compared to double vHPSD ablations (vHPSD + vHPSD, 3.4 [3.1–3.6] mm; vHPSD + AI 450 at 35 W, 4.4 [4.1–4.9] mm; vHPSD + AI 450 at 50 W, 4.5 [4.1–4.9] mm, p < 0.001). High‐power SA with a target AI of 550 created significantly deeper lesions than vHPSD + AI 450 (DA vs. SA, 4.5 [3.5–5.3] mm vs. 5.0 [4.1–5.9] mm, p = 0.01). Conclusions AI‐guided RF applications following vHPSD effectively increased lesion depth more than repeated vHPSD. However, a single high‐power application targeting a higher AI resulted in the deepest lesions. This strategy may be particularly beneficial in thick atrial myocardial regions to enhance lesion durability and improve procedural outcomes.